This research project proposes to develop instrumentation and techniques necessary for utilizing a new method of quantitating the factors that determine pulmonary gap exchange function in health and disease. This method is based on the theory and techniques of nonsteady-state (transient) exchange of multiple gases by the lung. The keystone of this project is the use of a sensitive and versatile quadrupole mass spectrometer to measure trace inert gas concentrations in both blood and gas streams during transient changes in these concentration levels. The primary significance of this research is in the development of mass spectrometer procedures for obtaining these transient measurements. At present, the transient inert gas data can be obtained only with a slow, cumbersome, batch-sample gas chromatographic technique. The mass spectrometer approach will allow rapid, almost continuous measurements of multiple inert gas exchange at tract concentration levels with a significant reduction in blood sample volume requirements. The transient multiple inert gas data will be analyzed and interpreted using the techniques of nonlinear parameter estimation. The results of this computer analysis will be estimates of the parameters of separate functional distributions of ventilation, perfusion, and gas and tissue volumes in the lung. These types of distributions provide new information on the mechanisms of pulmonary gas exchange function and dysfunction. In this research project the transient multiple inert gas technique will be applied in two specific areas in order to establish the mass spectrometer method and to obtain basic physiological data: measurement of distributions of ventilation, blood flow, and lung volumes in 1) awake and anesthetized dogs and 2) normal humans at rest and during exercise.